It is well established that adverse events (such as blood element or cell damage, thrombus formation, and platelet activation) can be caused by flow-induced shear stresses. These factors may seriously limit the performance of a broad range of devices used to transport biological fluids. By way of non-limiting example, such devices include cardiovascular hardware, prosthetic valves, stents, bypass pumps, and flow-assist devices as well as conduits for transporting such fluids. In particular, there exists a large body of scientific literature that has emphasized the significant risk associated when blood elements are subjected to non-physiological hemodynamic shear stresses in in-vivo devices (heart valves, flow assist devices etc.), and the severe limitations of non in-vivo devices (bypass pumps, dialysis machines, heart-lung instruments, or syringe needles, etc.).
Implanted ventricular assist devices (VADs) have also been implicated in thromboembolic events. Other known examples of blood damage in cardiovascular systems include centrifugal blood pumps that are used during bypass surgery and have been shown to cause hemolysis and platelet activation, which can lead to thromboembolism. Also, blood flow over surfaces of vascular stents (coronary or peripheral stents) can induce shear stress resulting in thrombus formation.
Shear stress can lead to coagulation and thromboemboli formation by either damaging the red blood cell (RBC) or by mechanically activating the platelet. High levels of shear stress can tear the RBC membrane, thus exposing tissue factor to the plasma and initiating the tissue factor pathway of the coagulation cascade. Shear stress can also trigger the coagulation cascade by activating platelets directly. Platelets are activated by shear stress that results in mechanotransduction of the force to a GP1b receptor.
This mechanotransduction enables binding of the GP1b receptor to Von Willebrand Factor (vWF) and a subsequent influx of calcium ions, resulting in platelet activation. Upon activations the GpIIb/IIIa receptor is activated and can then bind to other ligands such as fibrinogen, vWF, fibronectin, and vitronectin. The coagulation cascade is propagated and can lead to the formation of thrombin-anti-thrombin III (TAT), which is a relative measure of thrombin formation. RBCs are vulnerable to sub-lethal damage at shear stresses of 500 dynes/cm2 and by as little as 10-100 dynes/cm2 in the presence of foreign surfaces. In addition, platelet activation can occur at shear stresses as low as 60-80 dynes/cm2.
Flow stasis and recirculation regions have been shown to correlate to platelet deposition, particularly if these regions directly follow after a high shear stress region. The flow stagnation regions that occur at the blood-material interface on cardiovascular devices immediately adjacent to these high shear stress flow environments can promote damaged blood elements deposition, leading to thrombus formation on the cardiovascular devices.
Another important factor affecting the degree of blood damage is the amount of time the blood element spends in the high shear stress region. Shear-induced platelet activation and hemolysis are known to be a result of extended exposure of blood cells to high levels of shear stress. Previous studies have emphasized the importance of both stress magnitude and exposure time as important parameters in assessing shear related blood cell damage. The closing flow transients that occur during the leaflet closure phase are associated with the formation of a strong leakage jet in the B-datum region preceded by strong counter rotating starting vortices of high shear rates.
There exists a need for systems and methods for flow control devices that can minimize the magnitude of shear stresses experienced by blood elements. The flow control devices should counteract the formation of strong vortices thereby reducing the overall platelet activation potential of cardiovascular devices. In addition, the flow control devices should mitigate the adverse effects of high shear stress in blood-contacting devices and manipulate secondary vorticity concentrations within the blood flow. Furthermore, the flow control devices should enhance cross stream mixing and momentum transfer to diminish local velocity gradients and corresponding shear stress distributions.